Several studies have linked hepatic metallothionein (MT) synthesis to changes in zinc metabolism in response to various forms of stress and to administration of glucocorticoid hormones. There is also some evidence that the intestinal absorption of Zn is enhanced under such conditions. The present studies were designed to investigate the effect of dexamethasone on the kinetics of Zn uptake in an isolated segment of the adult rat jejunum, perfused through the lumen and maintained in situ. Dexamethasone administered to adrenalectomized rats was found to affect significantly one of the parameters of the equation describing 65Zn uptake. Because the observed effect was kinetically consistent with an increased synthesis of MT in the jejunal mucosa, the synthesis of MT was monitored with 35S-cystine in both the liver and intestine of adrenalectomized rats given dexamethasone. Under these conditions, MT synthesis was significantly increased in the liver but not in the jejunal mucosa. The results indicate that dexamethasone is able to alter the kinetics of Zn uptake in the jejunum, but does so without increased jejunal MT synthesis.